1. Field of the Invention
The invention is in the field of iontophoresis. In particular, the invention relates to awakening an electronic controller of an iontophoretic delivery device by the insertion of a drug delivery patch into the controller. The invention is also directed to a controller that prevents an electrical sensation upon the application of the drug delivery patch to the skin of a patient.
2. Description of Related Art
Iontophoresis is the migration of ions when an electrical current is passed through a solution containing ionized species, usually the ionic form of a drug or other therapeutic agent. One particularly advantageous application of iontophoresis is the non-invasive transdermal delivery of ionized drugs into a patient. This is done by applying low levels of current to a patch placed on the patient's skin, which forces the ionized drugs contained in the patch through the patient's skin and into his or her bloodstream.
Passive transdermal patches, such as those used to deliver nitroglycerin for angina pectoris, estradiol for hormone replacement, and nicotine to stop smoking, can only use a limited number of drugs because they work by diffusion. Iontophoresis advantageously expands the range of drugs available for transdermal delivery, including, for example, parenteral drugs (e.g., peptides). Further, because the amount of drug delivered is proportional to the amount of current applied, the drug delivery rate can be precisely controlled by controlling the current, unlike the passive transdermal patches. This allows for more rapid delivery (onset) and drug reduction (offset) in the patient.
When compared to drug delivery by needle injection, iontophoresis has less physical and emotional trauma, pain and possibility of infection. Transdermal drug delivery by iontophoresis also avoids the risks and inconvenience of IV (intravenous) delivery. In addition, when compared to oral ingestion of drugs, drug delivery by iontophoresis puts the drug directly into the bloodstream, bypassing the GI tract, thus reducing side-effects such as drug loss, indigestion and stomach distress and eliminating the need for swallowing the drug. Iontophoresis also avoids drug loss due to hepatic first pass metabolism by the liver that occurs when drugs are ingested.
Further, transdermal drug delivery by iontophoresis permits continuous delivery of drugs with a short half life and easy termination of drug delivery. Because iontophoresis is more convenient, there is a greater likelihood of patient compliance in taking the drug. Thus, for all of the above reasons, iontophoresis offers an alternative and effective method of drug delivery, and a especially useful method for children, the bedridden and the elderly.
An iontophoretic drug delivery device typically includes a current source, such as a battery and current controller, and a patch. The patch includes an active reservoir and a return reservoir. The active reservoir contains the ionized drug, usually in a conductive gel. The return reservoir contains a saline gel and collects ions emanating from the patient's skin when the drug is being delivered into the patient's skin.
The patch also has two electrodes, each arranged inside the active and return reservoirs to be in respective contact with the drug and saline. The anode, or positive, electrode and the cathode, or negative, electrode are respectively electrically connected to the anode and cathode of the current source by electrical conductors. Either the anode electrode or the cathode electrode is placed within the drug reservoir, depending on the charge of the ionized drug. This electrode is designated as the active electrode. The other electrode is placed within the return reservoir, and is designated as the return electrode.
The active electrode has the same charge as the ionized drug to be delivered and the return electrode has a charge opposite the drug to be delivered. For example, if the drug to be delivered to the patient has a positive ionic charge, then the anode will be the active electrode and the cathode will be the return electrode. Alternatively, if the drug to be delivered has a negative ionic charge, then the active electrode will be the cathode and the return electrode will be the anode. When current from the current source is supplied to the active electrode, the drug ions migrate from the drug gel in the reservoir toward and through the skin of a patient. At the same time, oppositely-charged ions flow from the patient's skin into the saline solution of the return reservoir. Charge is transferred into the return electrode and back to the current source, completing the iontophoretic circuit.
The electronic controller between the battery and the electrodes delivers the required current to the patch. The controller may control the output current so that drug delivery is accomplished at a constant or varying rate, or over a short, long or periodic time interval. These controllers generally require relatively complex electrical circuits, sometimes including microprocessors, to meet the above requirements. Conventional manually-operated mechanical switches have been used in controllers to disconnect the battery from the controller circuitry to prevent battery drain during device storage. See, for example, the switch disclosed in U.S. Pat. No. 4,808,152 (Sibalis).
These controllers need to be switched on at the time they are placed on the body in order to begin operating. This represents a potential opportunity for error in drug delivery because the physician, nurse or patient may not remember to turn on the switch, and may also inadvertently turn off the switch before completion of the drug delivery cycle. In addition, in the case of a defective switch or a switch having poor electrical contact, there may be uncertainty concerning whether or not the device is actually delivering the therapeutic agent, or can uninterruptibly complete an entire drug delivery cycle.
Moreover, in iontophoretic delivery devices that are switched on prior to placement on a patient, electric charge has the opportunity to build up on the electrodes. A mild, but discomforting electrical sensation may be felt by the patient upon placement of the patch onto the patient's skin from the discharge of built-up electric charge. Although not painful, this is likely to reduce compliance with a drug treatment program because the patient might be afraid to use the device in the future.
In one iontophoretic device shown in U.S. Pat. No. 5,314,502 (McNichols et al.), the device, including activation circuitry and power generating circuitry, remains completely turned off until the patch is applied to the skin. At that time, the activation circuitry closes and the power generating circuitry is turned on, thereby activating the device. Because the skin acts as the switch, no conventional mechanical switch is required. Other touch-sensitive switches have been disclosed in U.S. Pat. No. 4,099,074 (Maeda et al.) and G.B. Patent 1,321,863 (Reichart). However, a problem may still exist because the device may be activated when in contact with a conductor other than a patient's skin. If the device is placed on a conductive surface, the device will be activated resulting in the unnecessary waste of the therapeutic drug, and generate uncertainty in its ability to deliver the entire drug dosage. Moreover, because the circuitry is completely turned off until the patch is applied to the skin, the device shown in McNichols et al. cannot perform self-testing prior to the application of the patch to the skin.